Department of Psychology, University of California, Los Angeles, Psychology Building 1285, Box 951563, Los Angeles, CA, 90095-1563, USA.
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
Clin Epigenetics. 2022 Apr 8;14(1):48. doi: 10.1186/s13148-022-01269-9.
Altered DNA methylation (DNAm) may be one pathway through which early-life adversity (ELA) contributes to adverse mental and physical health outcomes. This study investigated whether the presence versus absence of ELA experiences reflecting the dimensions of threat and deprivation were associated with epigenome-wide DNAm cross-sectionally and longitudinally in a community-based sample of children and adolescents.
In 113 youths aged 8-16 years with wide variability in ELA, we examined associations of abuse (physical, sexual, emotional; indicating threat-related experiences) and neglect (emotional, physical; indicating deprivation-related experiences) with DNAm assessed with the Illumina EPIC BeadChip array, with DNA derived from saliva. In cross-sectional epigenome-wide analyses, we investigated associations of lifetime abuse and neglect with DNAm at baseline. In longitudinal epigenome-wide analyses, we examined whether experiencing abuse and neglect over an approximately 2-year follow-up were each associated with change in DNAm from baseline to follow-up.
In cross-sectional analyses adjusting for lifetime experience of neglect, lifetime experience of abuse was associated with DNAm for four cytosine-phosphodiester-guanine (CpG) sites (cg20241299: coefficient = 0.023, SE = 0.004; cg08671764: coefficient = 0.018, SE = 0.003; cg27152686: coefficient = - 0.069, SE = 0.012; cg24241897: coefficient = - 0.003, SE = 0.001; FDR < .05). In longitudinal analyses, experiencing neglect over follow-up was associated with an increase in DNAm for one CpG site, adjusting for abuse over follow-up (cg03135983: coefficient = 0.036, SE = 0.006; FDR < .05).
In this study, we identified examples of epigenetic patterns associated with ELA experiences of threat and deprivation that were already observable in youth. We provide novel evidence for change in DNAm over time in relation to ongoing adversity and that experiences reflecting distinct ELA dimensions may be characterized by unique epigenetic patterns.
改变的 DNA 甲基化（DNAm）可能是早期生活逆境（ELA）导致心理健康和身体健康不良后果的途径之一。本研究调查了在社区为基础的儿童和青少年样本中，反映威胁和剥夺维度的 ELA 经历的存在与否是否与全基因组范围内的 DNAm 存在横断面和纵向关联。
在 113 名年龄在 8-16 岁之间、ELA 差异较大的青少年中，我们使用 Illumina EPIC BeadChip 阵列检测了来自唾液的 DNA 中与虐待（身体、性、情感；表明与威胁相关的经历）和忽视（情感、身体；表明与剥夺相关的经历）相关的 DNAm 与生活史中虐待和忽视的关联。在全基因组范围的横断面分析中，我们研究了生活史中虐待和忽视与基线时 DNAm 的关联。在纵向全基因组分析中，我们检查了在大约 2 年的随访期间经历虐待和忽视是否分别与从基线到随访的 DNAm 变化相关。
在调整生活史中忽视经历的横断面分析中，生活史中虐待与四个胞嘧啶-磷酸二酯-鸟嘌呤（CpG）位点的 DNAm 相关（cg20241299：系数=0.023，SE=0.004；cg08671764：系数=0.018，SE=0.003；cg27152686：系数=-0.069，SE=0.012；cg24241897：系数=-0.003，SE=0.001； FDR<.05）。在纵向分析中，调整随访期间的虐待，随访期间忽视与一个 CpG 位点的 DNAm 增加相关（cg03135983：系数=0.036，SE=0.006；FDR<.05）。
在这项研究中，我们确定了与威胁和剥夺相关的 ELA 经历相关的表观遗传模式的例子，这些模式在年轻人中已经可以观察到。我们提供了关于与持续逆境相关的 DNAm 随时间变化的新证据，并且反映不同 ELA 维度的经历可能具有独特的表观遗传模式。
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